Protective effects of 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ols against 4-hydroxynonenal-induced cell death in adult retinal pigment epithelial-19 cells
- Authors
- Bae, Dawon; Gautam, Jaya; Jang, Hyeonjin; Banskota, Suhrid; Lee, Sang Yeul; Jeong, Min-Ji; Kim, A-Sol; Kim, Hong Chul; Lee, Iyn-Hyang; Nam, Tae-gyu; Kim, Jung-Ae; Jeong, Byeong-Seon
- Issue Date
- Jan-2018
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- Retinal pigment epithelium; Apoptosis; NADPH oxidase 4; 6-Ureido/thioureido-2,4,5-trimethylpyridin-3-ol; 4-Hydroxynonenal
- Citation
- BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, v.28, no.2, pp.107 - 112
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
- Volume
- 28
- Number
- 2
- Start Page
- 107
- End Page
- 112
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/6860
- DOI
- 10.1016/j.bmcl.2017.11.046
- ISSN
- 0960-894X
- Abstract
- Dysfunction or progressive degeneration of retinal pigment epithelium (RPE) contributes in the initial pathogenesis of age-related macular degeneration (AMD) causing irreversible vision loss, which makes RPE the prime target of the disease. The present study aimed to identify compounds to protect 4-hydroxynonenal (4-HNE)-induced RPE cell death by inhibiting NADPH oxidase 4 (NOX4) activity, not just as free radical scavengers, using ARPE-19, a human adult retinal pigment epithelial cell line, as a RPE representative. Novel thirty-two 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ol derivatives 17 were synthesized and tested. We found that there was a strong correlation between level of protective effect of compounds 17 against 4-HNE-induced APRE-19 cell death and that of inhibitory activity against 4-HNE-induced superoxide production, and that most of the compounds 17 showed minimal DPPH radical scavenging activity. Compound 17-28 showed the best protective activity against 4-HNE-induced superoxide production (79.5% inhibition) and cell death (85.1% recovery) at 10 mu M concentration, which was better than that of VAS2870, a NOX2/4 inhibitor. In addition, compound 17-28 blocked 4-HNE-induced apoptosis of ARPE-19 cells in a concentration-dependent manner. The results indicate that compound 17-28 may be a lead compound to develop AMD therapeutics. (C) 2017 Elsevier Ltd. All rights reserved.
- Files in This Item
-
Go to Link
- Appears in
Collections - COLLEGE OF PHARMACY > DEPARTMENT OF PHARMACY > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/6860)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.